Genetic Research Could Hold the Key to Better Therapies

BY

May 12 2006 12:00 AM ET

While there have been numerous advances in HIV treatment since the first AIDS cases were reported 25 years ago, all of them have focused on the virus itself'either in thwarting its ability to copy itself or preventing it from infecting vulnerable immune system cells. But a new field of experimental treatment is emerging from laboratories across the country that is turning away from the virus and focusing instead on improving defenses against it.

Researchers in San Francisco have reported that they are studying the combined use of stem cell technology and genetic engineering to create a 'parallel immune system' in about 70 HIV-positive adults. They accomplish this by inserting an engineered enzyme that blocks HIV replication into immune system stem cells collected from the blood of the study participants. The enhanced stem cells are then reinjected into the patients, where they begin to produce an array of blood cells primed to shut down any attempts by HIV to hijack cellular machinery and copy itself.

If successful, the therapy could create a long-lived natural defense against HIV and potentially even allow HIVers to stop taking antiretroviral medications.
'It's possible that the stars are lining up with this one,' University of California, San Francisco, researcher Jay Lalezari told the San Francisco Chronicle. More complete clinical trial data will be available in February 2007.

Ohio State University scientists in March reported the discovery of two human proteins'called XPB and XPD'that appear to destroy HIV genetic material. Their lab tests showed that HIV-infected cells with higher levels of the proteins were significantly less likely to be producing viral copies due to the proteins' ability to disrupt HIV's genetic material before it is integrated into cellular DNA, a key step in the viral replication process. HIV replication continued unchecked in cells in which the researchers inhibited XPB and XPD.

The research team is now working to learn exactly how the proteins shut down HIV's attempts to integrate into human cells, with the goal of developing new protein-based treatments built on their findings. And because such therapies would focus not on the virus itself but on the body's defenses against it, HIV would be far less likely to be able to mutate resistance to them, the researchers say.

'This approach does sound interesting, as it works at a very early stage in the life cycle of the virus,' AIDS expert Mary Lima of the British AIDS organization Terrence Higgins Trust told BBC News. 'The more opportunities we have to attack the HIV virus, the better.'